Zika, Chikungunya & Dengue: Update...José Darío Martínez, MD, FAAD Zika, Chikungunya & Dengue: Update DISCLOSURES I do not have any relevant relationships with industry. DISCLOSURE

Zika, Chikungunya & Dengue: Update

José Darío Martínez, MD, FAADInternal Medicine & Dermatology

Chief, Internal Medicine Clinic

University Hospital “JE González”, UANL

Monterrey, México

José Darío Martínez, MD, FAAD

Zika, Chikungunya & Dengue: Update

DISCLOSURES

I do not have any relevant relationships with industry.

DISCLOSURE OF RELATIONSHIPS WITH INDUSTRY

Travelers´ diseases

Medical problems in returned travelers Fever

Acute diarrhea

Skin lesions

Most common skin lesions are: Cutaneous larvae migrans

Insect bites (bedbugs)

Bacterial infections

Rash

Rash & fever in travelers

Most common causes in the Americas Malaria

Dengue fever

Spotted fever (rickettsia)

Yellow fever

West Nile fever

Chikungunya fever

Zika fever

Travelers´ maladiesAm J Clin Dermatol 2016 Oct;17(5):451-462

Zika, Chikungunya & Dengue

Update focus on: Zika: transmission, muco-cutaneous

manifestations, fetal malformations, diagnosis

CHIKF: cutaneous and articular manifestations

Dengue: prevention, new vaccine

Tables showing:

Similarities, differences, complications, prevention

Zika feverOverview Emerging mosquito-borne pathogen

Flavivirus

Was isolated in Zika forest in Uganda in 1947

Transmitted by Aedes aegypti mosquito

First epidemic occurred in 2007

in Micronesia

Emerging Infect Dis 2015;21(1):84-86

Zika feverEpidemiology During 2007-2013 few cases in travelers returning

from Africa or SE Asia were reported

First cases of ZF in The Americas were reported

in Brazil in 2015


Vasievich MP, Martínez JD, Tomecki KJ.

Am J Clin Dermatol 2016, DOI 10.1007/s40257-016-0203-7

Zika feverTransmission Mosquito bite

Mother-to-fetus

Sexual intercourse

Blood transfusion

Breast-feeding?

CDC, 2016

Zika feverClinical facts Asymptomatic in most cases (misdiagnosed)

Incubation period: 3-8 days

Mild fever (37.8 °C-38.5 °C)

Arthralgia (small joints in hands & feet): 65%

Headache, retroorbital pain

JAMA Dermatol 2016 DOI:10.1001/jamadermatol 2016.1433

Zika feverMuco-cutaneous signs Skin rash: 90%

Nonpurulent conjuntivitis: 55%

Oral enanthem

Pruritus

JAMA Dermatol 2016

DOI:10.1001/jamadermatol 2016.1433

Zika feverDiagnosis Serum RT-PCR: rapid, sensitive, and specific test

(first week)

Ab anti ZV: IgM & IgG (second week): cross

reaction with Dengue

TrioPlex Real-time RT-PCR

CDC’s new text for DF, CHIKF & ZF (Sept. 21,2016)

Not FDA approved yet, only in emergencies


Zika feverDiagnosis Urine RT-PCR: useful in travelers (2 weeks)

In pregnant women:

Fetal ultrasound

Amniocentesis (RT-PCR)


CDC: Zika fever recommendations in pregnant women, 2016

Zika feverDDX Dengue fever

Chikungunya fever

Viral rash

Drug reaction


Zika feverComplications

Neurologic: Guillain-Barré syndrome

Incidence difficult to asses

Microcephaly: most feared in pregnant women

during the first trimester (weeks 12-16)

Most cases reported in Brazil

About 5% of zika cases in pregnant

women in US (PR) had birth defects*

MMWR CDC, June 16, 2017*

Zika CDC map (December 14, 2016)

Zika fever

Public health strategies

Focused in A. aegypti that thrives and breeds

close to homes (water filled containers)

Meanwhile A. albopticus breeds in less accesible

areas (water filled leaves of plants)

These facts lead us to a difficult

vector erradication

A. alboticus tends to displace A. aegyptiVector borne and Zoonotic Diseases, 2016;16(2)

Zika feverPrevention & treatment Essential in pregnant women (or unaware)

Appropiate clothing and use of repellents (DEET)

Counselling before travel (travelers´disease)

Acetaminophen

Supportive therapy as needed

If pregnant: US, then amniocentesis

to detect transplacental ZV disease

Zika: microcephaly

Fundidora Park, Monterrey, México

Chikungunya feverOverview Alphavirus: Togaviridae virus (RNA)

Three serotypes (Asian, E/C/S African and W

African)

Chikungunya: african word (Makonde dialect)

which means “that which bends up”

Unlike DF, CHIKF results in greater and

prolonged morbidity than mortalityMed Clin N Am 2012;96:1225-1255

Chikungunya fever

Vector Female mosquito

Aedes aegypti

Aedes albopictus (Asian tiger mosquito)

Daylight: dawn & dusk

Outdoors (A aegypti indoors also)

Transmission: infected person to healthy person

(via mosquito bite)

Chikungunya fever vectors: Aedes aegypti & Aedes albopictus

Chikungunya fever

Epidemiology Came from Africa, India, Indonesia

Arrive to America on Dec. 2013

Caribbean islands (first cases)

March 2014: > 8000

cases

Travelers´disease

Spreading rapidly into The Americas

Chikungunya fever

Key facts It is transmitted by A aegypti

CHIKV strains mutate

Outbreak: La Reunion Island (2005-06)

Facilitating transmission by A albopictus

Mutation in the viral envelope gene E1

Very high ability to adapt to various environments

Movement of goods and people

Chikungunya fever

World cases as of 1952 to 2006

CHIKF in The Americas!Hot spots: Central America, Haiti, Dominican Republic,

Colombia, Venezuela, and Brazil

June, 2015 (PAHO)

366,000 SC

10,800 CC

54 deaths

December 30, 2015

México: 11,199

local cases (PAHO)

México City: 160 cases

Casualties unknown

CHIKV in US 2015June 1, 2016 (First local case reported in Brownsville, Texas since 2014)

Table 1. Laboratory-confirmed chikungunya virus disease cases reported to ArboNET by state—United States, 2015 (as of February 24, 2015)

State

Travel-associated cases(N=43)

Locally-transmitted cases (N=0)

No. (%) No. (%)

Arkansas 1 (2) 0 (0)

Colorado 1 (2) 0 (0)

Florida 12 (28) 0 (0)

Indiana 1 (2) 0 (0)

Kentucky 2 (5) 0 (0)

Maryland 4 (9) 0 (0)

Missouri 3 (7) 0 (0)

New Jersey 3 (7) 0 (0)

New York 9 (21) 0 (0)

Ohio 1 (2) 0 (0)

Pennsylvania 2 (5) 0 (0)

Texas 3 (7) 0 (0)

Washington 1 (2) 0 (0)

Chikungunya fever

Clinical picture 3-28% patients are asymptomatic

4 of 5 patients have symptoms

Incubation period: 7 days (1-12)

Fever

Arthritis

Muscle pain, headache

Chikungunya fever

Skin lesions Maculopapular rash

50% of cases

2-5 days after fever starts

Acral rash

Melanosis

Melanonichia

Vesicles, bullae

Genital ulcers

Chikungunya fever

Articular involvement Acute: high fever, arthralgia/arthritis, migrating

polyarthralgia, symmetric affection, no bleeding

(last 3-10 days)

Subacute: 2-3 months after, distal polyarthritis,

depression, fatigue, weakness

Chronic: arthralgia > 3 months, mimicking

RA/PsA (93% [3m], 53% [15m], 47% [24m])

Chikungunya fever

Risk factors for severe disease Newborns

Older age (> 65 years)

Co-morbidities like DM, HBP, HD

Pre-existing joint disease

Initial severe acute disease

Chikungunya fever

Diagnosis RT-PCR: most sensitive, rapid test, can detect

CHIKV in the first week

Serology: MAC-ELISA: IgM (+ in 2-6 days)

Serology: CHIKV IgG 4-fold elevation (+ in 7 days,

can last for years)

Eur J Int Med 2012;23:325-329

Chikungunya fever

DDx Dengue

Zika

Malaria

Leptospirosis

Menigococcemia

Drug eruption

Chikungunya fever

Treatment No vaccine available

No specific antiviral treatment

Acetaminophen (drug of choice)

NSAID’s

Bed rest (mosquito net)

Fluids

Eur J Int Med 2012;23:325-329

Chikungunya fever

Complications Articular chronic pain like RA/PsA

MTX has been used for chronic arthritis in Europe

Can affect unborn babies

Low mortality

No second infection

Can detonate autoimmune diseases ► SLE

Mortality associated with comorbidities

CHIKV CDC (April 22, 2016)

Palace of Fine Arts, México City

Dengue fever

Overview Warm climate, rainy season

Dengue virus (flavivirus)

Aedes aegypti mosquito

Female mosquito (bites in daytime)

Most prevalent arthropod-borne virus

Emerging disease

Illness can go from mild to fatal disease

Dengue mosquito

Dengue fever

Dengue virus sero-types DENV 1-4 (RNA virus)

DENV1 (most common)/DENV 2, 3 (more severe)

Dengue fever

Epidemiology Worldwide

2.5 billion people at risk

DENV cause 50-100 million cases of DF

250-500,000 cases of DHF per year

25,000 deaths per year

US: Texas outbreak (25 cases) occurred in 2005

México 2016 PAHO: >200,000 C/31 D/4 Sero-types

Dengue map 2016 (CDC)

Dengue fever

Clinical facts 60-80% dengue cases are asymptomatic

Incubation period: 2-8 days

Acute febrile illness: headache, high fever,

myalgia, arthralgia (“breakbone” fever), retro-

orbital pain, fatigue

Faint macular rash (2-6 days into illness)

Gums bleeding, nosebleeds, bruising

WHO definition of dengue fever: probable caseTravel Med and Infect Dis 2009;7:278-283

Acute febrile

illness (2 or +)

Headache

Retro-orbital

pain

Myalgia

Arthralgia

Rash

Hemorrhagic

manifestations

Leukopenia

Serology (+)

Dengue fever

Clinical syndromes (WHO)

Approximately 1% of patients will

progress to one of these during the critical

phase in days 4-7 of illness:

Dengue hemorrhagic fever (DHF)

Dengue shock syndrome (DSS)

J Emergency Med 2013;45(4):526-529

Dengue fever

Warning signs of severe disease

Abdominal pain

Persistent vomiting

Pleural effusion or ascites

Mucosal bleeding

These signs may ocurr at or after defervescence

DHF or DSS may be evolvingClev Clin J Med 2012;79(7):474-482

Dengue

Diagnosis Clinical suspicion

Travel to endemic areas (2 weeks before)

Serologic tests to detect antidengue Ab

IgM (positive at day 5 of illness)

IgG (recurrent infection)

RT-PCR (first 4-5 days)

NS1 (rapid test)

Dengue

DDx

Chikungunya fever

Zika

Malaria

Leptospirosis

Menigococcemia

Drug eruption

Dengue

Prevention Vaccine: not approved by the FDA yet

Use of repellents (DEET) on exposed skin

and/or clothing

DEET

Not for infants (< 2 months old)

Children and adults: DEET (15-30%),

no more than 30% in small children

Dengue Fever Vaccine!N Engl J Med 2015;372:113-123

Original ArticleEfficacy of a Tetravalent Dengue Vaccine in Children in LatinAmericaMethods: Children 9-16 yrs old, from Colombia, Brazil, México, Puerto Rico, and Honduras, in June 2011 to March 2012. Doses 0, 6, 12 months.Results: > 20,800 children (2/3 vaccine, 1/3 placebo), vaccine safety was good.Discussion: 60.8% overall efficacy, works well in all 4 serotypes, 80.2% vs. hospitalization, and 95.5% vs. severe dengue cases.Protection against DF starts with the first dose, but two more doses are needed to increase the Ab response and long lasting protection.Note: in México this vaccine was approved by Cofepris (12/9/15)

Dengvaxia: tetravalent vaccine

Dengue

Key points to avoid spread DF Avoid sick patient to get a bite from healthy

mosquitoes

Use of mosquito nets among sick patients

In travelers usually it is a mild disease

Patients with DF history can have the next time a

more severe form of DF

Dengue vaccine has been approved in México

& Brazil

Prevention (spray) with Avate:

cypermethrine and boric acid

Dengue

Management

Dengue fever: Bed rest, liquids

Isolation (mosquito net)

Actaminophen

DHF/DSS: Hospitalization

ICU

Supportive care

Dengue inpatient management

DF, CHIKF & ZF: clinical similaritiesTable by José Darío Martínez, MD

Feature Dengue Chikungunya Zika

Vector Aedes aegypti Aedes aegypti Aedes aegypti

Geo Area Worldwide Worldwide Worldwide

Incubation 2-8 days 1-12 days 3-8 days

Asymptomatic 60-80% <30% >80%

Fever ≥39 °C +++ +++ ++

Rash + ++ +++

Arthralgia/myalgia +/++ +++/+ ++/+

Vaccine Yes (Not FDA app) No No

Prevention DEET DEET DEET

DF, CHIKF & ZF: clinical & lab differencesTable by José Darío Martínez, MD


Bleeding ++ - -

Eyes/face Pain Melanosis Red eye, pain

Arthritis - +++ ++

Itch ++ + +++

Lymphopenia ++ +++ +

Neutropenia +++ + +

Thrombocytopenia +++ + +

DF, CHIKF & ZF: complications & RxTable by José Darío Martínez, MD


Chronic arthritis - + -

Guillain-Barré - - +

Shock + - -

STD - - +

Blood

transfusion

- - +

Microcephaly - - +

Recurrence + - -

Rx Supportive Supportive Supportive

Advertising at the airports & in the streets

in México!

DF, CHIKF, ZF

Summary

These mosquitoes can cause significant morbidity

and mortality among international travelers

Counseling to travelers

Prevention is basic

Clinicians must be aware of clinical presentation

CHIKV & ZF are emerging diseases in The

Americas

Serology confirmation is essential

DF, CHIKF, ZF

Summary

No vaccines approved by the FDA yet

In México & Brazil a DF vaccine was approved

CHIKV cycle last longer than DV

Zika is more dangerous than DF & CHIKF

Rx: acetaminophen, supportive therapy

Genetic modified mosquitoes introduced in Brazil

What is next? Mayoro virus? Yellow fever?

Email: [email protected]

Dermatology & Baseball…

Thank you! Gracias!Email: [email protected]

El Castillo, Chichen Itzá, Yucatán, México

Zika, Chikungunya & Dengue: Update...José Darío Martínez, MD, FAAD Zika, Chikungunya & Dengue: Update DISCLOSURES I do not have any relevant relationships with industry. DISCLOSURE

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